Dopamine in the Pathophysiology and Treatment of Schizophrenia: New Findings

Few paradigms in psychiatry have shown the resilience of the dopamine hypothesis of schizophrenia. Thirty years after the demonstration that the blockade of dopamine receptors is the common denominator underlying the effects of antipsychotic drugs, this neurotransmitter system remains at the heart of current research. In 2002, on the 50th anniversary of the introduction of antipsychotics, a meeting was held in Montreal, gathering European and North American leaders in the field of dopamine and schizophrenia research, who shared and updated current knowledge on the subject. The results of this enterprise are embodied in pages of this attractive yet dense book.

The 12 chapters, each by different authors, offer a comprehensive picture of the present state of research. A number of different topics and points of view are brought up, sometimes stirring controversy between the authors. This book provides, among other material, a summary of the historical background of the dopamine hypothesis and its successive formulations, showing that we are a long way from the first formulations, which implied, somewhat naively, that schizophrenia can be reduced to dopamine mesolimbic hypersecretion. The chapter authors caution against such a monolithic view, and the content of the book reflects this concern.

Plausible models of interaction between dopamine and glutamatergic systems are described in chapters 1 and 2, and the importance of other neurotransmitter systems and receptors, especially serotonin, is detailed in chapter 9. Abi-Dargham reviews the recent evidence from brain imaging studies pointing toward a dopamine imbalance at a limbic level and once more confirming the role of dopamine in schizophrenia. As one would expect, the current hypotheses about the neurobiological basis of atypicality are explored, especially the apparent paradox of amisulpride, which has a strong and almost exclusive affinity to dopamine receptors while behaving clinically like an atypical antipsychotic. The authors posit that amisulpride, which is widely used in Europe but unavailable in North America, could offer some advantage in the treatment of negative symptoms in maintenance therapy. Furthermore, an inspiring reflection about a probable genetic mechanism of risk for schizophrenia, involving variations in the COMT gene, is put forward by Weinberger in chapter 7.

The dopamine hypothesis may also offer an understanding of clinical phenomena, as outlined by Kapur and, albeit in a wider frame, Spitzer. The dopamine system plays a central role in the attribution of salience, a psychological mechanism by which the brain filters and labels important information. Chapter authors stress the idea that dopamine dysfunction, for this reason, could constitute a primary mechanism for the elaboration of delusions and delusional perceptions, eloquently bridging the apparent gap between neuroscience and psychology. Stahl provides an inspiring conclusion that reviews the unmet needs in the treatment of schizophrenia.

Overall, this is a very instructive piece of work, successfully depicting the current state of knowledge regarding the dopamine hypothesis and opening avenues of research and reflection. Exhaustiveness has been preferred to uniformity, making it a heterogeneous work. However, one could argue that it is representative of our relative ignorance on the matter, where there is ample space for controversy and generation of new hypotheses eliciting original and diversified angles of approach. Although some chapters may seem at first glance tedious to the neophyte, this book is undoubtedly a must-read for clinicians and researchers alike who want to better their knowledge of dopamine’s role in schizophrenia.